CN1088358C - 含有镇咳药和苄达明的镇咳组合物 - Google Patents

含有镇咳药和苄达明的镇咳组合物 Download PDF

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CN1088358C
CN1088358C CN95191917A CN95191917A CN1088358C CN 1088358 C CN1088358 C CN 1088358C CN 95191917 A CN95191917 A CN 95191917A CN 95191917 A CN95191917 A CN 95191917A CN 1088358 C CN1088358 C CN 1088358C
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pharmaceutically acceptable
benzydamine
compositions
acceptable salt
dextromethorphan
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CN1143909A (zh
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D·加里·安杰利
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Angelini Acraf SpA
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Aziende Chimiche Riunite Angelini Francesco ACRAF SpA
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/14—Antitussive agents

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Abstract

一种镇咳药物组合物，它能使其成分与颊面洞的粘膜有效接触，并含有中枢作用镇咳药或其药学上可接受的盐和苄达明或其药学上可接受的酸加合盐。

Description

含有镇咳药和苄达明的镇咳组合物
本发明涉及一种镇咳组合物。
更具体地讲，本发明涉及一种口服镇咳组合物，其特征在于它含有一种中枢作用镇咳药或其药学上可接受的盐和苄达明或其药学上可接受的酸加合盐。
咳嗽是一种有助于从呼吸道消除异物和过量分泌物的生理动作。但有时咳嗽达不到有利的目的反而打搅病人或妨碍他或她休息或睡觉。这就导致需要服用减小咳嗽频率和/或严重性的药物。
在减咳的许多药物中有些作用于中枢神经系统。这种镇咳药的实例有：可待因、右美沙芬、二氢可待因、二甲啡烷、诺司咳平、萘磺酸左旋丙氧吩、咳必清、卡拉美芬、氯苯达诺、苯海拉明、海罂粟碱、苯佐那酯、氢可酮和二氢吗啡酮。其中最常用的是：可待因、右美沙芬、二氢可待因、二甲啡烷和诺司咳平。
右美沙芬是非麻醉中枢作用镇咳药的一个特别显著的例子(TheMerck Index，9th ed.，1976，p1289，No.8116)。右美沙芬氢溴酸盐对成人的平均剂量是15-30mg，每日3-4次(Goodman & Gilman-“Lebasi farmacologiche della terapia”-意大利文第8版，Zanichelli-Bologna)。有糖锭剂、片剂、糖浆和滴剂，单独使用或与香脂-祛痰药合用。
苄达明(The Merck Index，第9版，1976，p147 No.1136)首次公开于US-3318905中，该专利涉及一组具有止痛、消炎和肌肉松驰作用的物质。苄达明以盐酸盐形式已广泛用于人体治疗。对全身性途径给药而言它主要用作消炎止痛药，但对表皮途径而言主要用于涉及局部炎症的那些病症，如肌痛、腱炎、外阴阴道炎、龈炎、胃炎、颊面洞的粘膜炎症等。
现意外地发现苄达明和其药学上可接受的酸加合盐，与单用镇咳药相比，在特别的病理中能够缩短中枢作用镇咳药对咳嗽外周刺激的起始作用时间。
这一意外效果已被人体临床试验所证实。
因此，本发明的第一个目的是提供一种口服镇咳药物组合物，其特征在于：
-它能使其成分与颊面洞的粘膜有效接触，
-含有一种中枢作用镇咳药或其药学上可接受的盐和苄达明或者药学上可接受的酸如合盐。
例如，右美沙芬单用时在20-30分钟内起作用(H.Matthys，B.Bleieher et al.，J.Int.Med.Res.，11，92-100，1983)。
但是当右美沙芬在与苄达明或其药学上可接受的酸加合盐联合、并以能使其成分与颊面洞的粘膜有效接触的药物剂型给药时，它在很短的时间内就能减小咳嗽症状，即在数分钟内。
能使其成分与颊面洞的粘膜有效接触的合适的药物剂型，其实例有锭剂、甜食、可嚼片剂和橡皮糖。
除苄达明或其酸加合盐(如盐酸盐)和中枢作用镇咳药或其药学上可接受的盐以外，本发明组合物还含有固态或液态惰性赋形剂或载体，以及任选的其他适合药用的添加剂，并按常规技术制备。
适合的添加剂例如是甜味剂、香料和染料。
本发明组合物中苄达明和中枢作用镇咳药的有效剂量取决于各种因素，这是本领域技术人员熟知的，例如所用镇咳药、个体反应、病人的年龄和总体健康状况。
但一般而言，本发明组合物含有0.5-2倍于标准剂量的中枢作用镇咳药或相当量的其药学上可接受的盐。
“标准剂量”在本说明书中指每个个别中枢作用镇咳药通常口服给药时的有效剂量。
例如，右美沙芬的有效剂量范围根据治疗对象是儿童或成人，为每次给药5-30mg(每日1-6次)。但有时单剂给予60mg(Goodmen& Gilman，意大利文第7版，p486)。
对于苄达明，使用已证明能够缩短中枢作用镇咳药对咳嗽外周刺激的起始作用时间的量，这根据具体镇咳药和药物剂型而不同。
对苄达明而言典型情况是，本发明药物组合物含有(a)中枢作用镇咳药重量1/200到2倍的量，或(b)相当量的其药学上可接受的酸加合盐。
本发明第一种优选组合物含有0.15-10mg苄达明和5-30mg右美沙芬或相当量的其药学上可接受的盐。
最后，本发明药物组合物还可以含有已知与中枢作用镇咳药合用的其他活性成分。
所述活性成分的典型实例是抗组胺药和香脂药剂。
下列实施例用于说明本发明但不限制其范围。
实施例1可嚼片剂每个1.37g片剂含：盐酸苄达明              3.0mg水合右美沙芬氢溴酸盐    7.5 mg甘露醇                  1121.5mg麦芽酚                  200.0mg三硅酸镁                67.5mg硬脂酸镁                15.5mg甘草酸铵                15.0mg阿司帕坦                15.0mg香脂香料                15.0mg甘油棕榈酸硬脂酸酯      10.0mg
按直接压制法制备该片剂；将活性成分预混合以保证在最终产品中含量均一。
将麦芽酚和部分甘露醇置于一ZanchettaTM混合器中。
将吸附在10％三硅酸镁上的盐酸苄达明和单水右美沙芬氢溴酸盐置于一较小的混合器中，然后加入香脂香料、阿司帕坦、甘草酸铵和其余的甘露醇。
将此混合物混合约15分钟，然后转移到含甘露醇和麦芽酚的混合器中。
然后加入硬脂酸镁和甘油棕榈酸硬脂酸酯，混合约30分钟至均匀。
用装有冲头(20.5×11.5mm)的旋转机压制此混合物。
实施例2甜食每5g甜食含有：盐酸苄达明          3.0mg右美沙芬氢溴酸盐    7.5mgLycasin 80/55       4165.0mg阿拉伯胶            79.0mg甘露醇              725.0mg天然香料            20.3mg天然染料            0.2mg
实施例3甜食每5g甜食含有：盐酸苄达明          3.0mg右美沙芬氢溴酸盐    7.5mg蔗糖                3052.5mg葡萄糖              1920.0mg薄荷                12.0mg薄荷醇              4.8mg天然染料            0.2mg

Claims (8)

1.一种口服镇咳药物组合物，其特征在于它含有一种中枢作用镇咳药或其药学上可接受的盐和苄达明或其药学上可接受的酸加合盐。
2.权利要求1的组合物，其特征在于它呈锭剂、甜食、可嚼片剂或橡皮糖形式。
3.权利要求1或2的组合物，其特征在于其含有0.5-2倍于标准剂量的、选自下组的中枢作用镇咳药：可待因、右美沙芬、二氢可待因、二甲啡烷、诺司咳平、萘磺酸左旋丙氧吩、咳必清、卡拉美吩、氯苯达诺、苯海拉明、海罂粟碱、苯佐那酯、氢可酮和二氢吗啡酮及其药学上可接受的盐。
4.权利要求1或2的组合物，其特征在于它含有1/200到2倍于中枢作用镇咳药重量的苄达明或相当量的其药学上可接受的加合盐。
5.权利要求1的组合物，其特征在于它含有0.15-10mg苄达明和5-30mg右美沙芬或相当量的其药学上可接受的盐。
6.权利要求5的组合物，其特征在于苄达明的药学上可接受的盐是盐酸盐。
7.权利要求5或6的组合物，其特征在于右美沙芬的药学上可接受的盐是氢溴酸盐。
8.权利要求5或6的组合物，其特征在于右美沙芬的药学上可接受的盐是水合氢溴酸盐。
CN95191917A 1994-03-01 1995-02-22 含有镇咳药和苄达明的镇咳组合物 Expired - Fee Related CN1088358C (zh)

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ITMI94A000362 1994-03-01
ITMI940362A IT1274026B (it) 1994-03-01 1994-03-01 Composizione antitosse

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US6124282A (en) * 1997-05-22 2000-09-26 Sellers; Edward M. Drug formulations
CA2314893C (en) * 1997-12-22 2005-09-13 Euro-Celtique, S.A. Opioid agonist/antagonist combinations
US7138133B2 (en) 2001-10-10 2006-11-21 The Procter & Gamble Company Orally administered liquid compositions
WO2003089007A1 (en) * 2002-04-22 2003-10-30 Adcock Ingram Intellectual Property (Proprietary) Limited Pharmaceutical compositions comprising a decongenstant and further active ingredients for treating cough and flu
PL1848403T3 (pl) * 2005-01-14 2010-09-30 Camurus Ab Preparaty bioadhezyjne o działaniu miejscowym
SI1845942T1 (sl) * 2005-01-14 2014-06-30 Camurus Ab Gnrh analogne formulacije
CN101219140B (zh) * 2007-12-24 2011-06-01 重庆市莱美药物技术有限公司 盐酸苄达明可溶片及其制备方法
SI2451452T1 (sl) 2009-07-08 2015-12-31 Aziende Chimiche Riunite Angelini Francesco - A.C.R.A.F. - S.P.A. Uporaba benzidamina pri zdravljenju bolezni, odvisnih od p40
CA2904045C (en) * 2013-03-13 2022-03-29 Tris Pharma, Inc. Benzonatate modified release solid tablets and capsules
CA2976187A1 (en) * 2015-02-09 2016-08-18 Cellix Bio Private Limited Benzydamine salts and compositions thereof useful for the treatment of mucositis
US11214544B2 (en) 2017-04-14 2022-01-04 Kempharm, Inc. Dextrorphan prodrugs and processes for making and using them

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WO1992007559A1 (en) * 1990-10-31 1992-05-14 The Procter & Gamble Company Dextromethorphan antitussive compositions

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US5196436A (en) * 1990-10-31 1993-03-23 The Procter & Gamble Company Dextromethorphan antitussive compositions

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WO1992007559A1 (en) * 1990-10-31 1992-05-14 The Procter & Gamble Company Dextromethorphan antitussive compositions

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CA2184594A1 (en) 1995-09-08
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ZA951588B (en) 1995-12-08
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WO1995023602A1 (en) 1995-09-08
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DK0748222T3 (da) 2000-12-18
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HU9602390D0 (en) 1996-10-28
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SK282567B6 (sk) 2002-10-08
ITMI940362A0 (it) 1994-03-01
ES2149969T3 (es) 2000-11-16
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SK108596A3 (en) 1997-04-09
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